ALTERED PREFRONTAL CORTICAL SEROTONERGIC NEUROTRANSMISSION IS ASSOCIATED WITH POST-WEANING SOCIAL ISOLATION-INDUCED ABNORMAL SOCIAL BEHAVIOUR
01/30/2020
Huba Szebik1, László Biró1, Christina Miskolczi1, 2, Bíborka Bruzsik1, 2, Orsolya Horváth1, Zoltán Kristóf Varga1, 2, László Szente1, 2, József Halász1, Máté Tóth1, Éva Mikics1
1 Institute of Experimental Medicine, Translational Behavioural Neuroscience, Budapest, Hungary
2 Janos Szentagothai Doctoral School of Neurosciences, Semmelweis University, Budapest
Early-life adversities are major risk factors for developing antisocial behaviors during adulthood. Here, we applied the post-weaning social isolation model to investigate the neuronal background of behavioral abnormalities induced by early-life social isolation. Mice were isolated or housed socially (4/cage) from weaning (P21) until adulthood. Aggressive behavior in adulthood was assessed in the resident-intruder test, where isolated mice showed abnormal aggressive behavior. Mice were perfused 90 minutes after the resident-intruder test, and additional animals were perfused in resting state. Neuronal activity of the prefrontal cortex (PFC) – a brain region with protracted developmental trajectory and importance in controlling social behavior – was assessed by c-Fos immunohistochemistry. Fighting by itself increased neuronal activation in the medial PFC, and social isolation caused hyperactivation of the medial PFC compared to group-housed animals. To investigate changes in the serotonergic system, a neuromodulator that plays a major role in controlling both social behavior and prefrontal activity, we performed immunohistochemical staining against 5-HT and SERT, the key protein involved in 5-HT reuptake. Surprisingly, the density of both SERT and 5-HT increased in the medial PFC of animals participating in the resident-intruder test. Although we did not observe any rearing-specific changes in SERT or 5-HT fiber density, SERT density showed positive correlation with behavioral parameters of aggressive behavior in isolated animals, which was absent in group-housed littermates. In conclusion, early-life social isolation leads to abnormally aggressive behaviour during adulthood, and this is associated with the neuronal hyperactivation of the prefrontal cortex, which is associated with disturbed serotonergic signaling.